BIOLOGICAL EVALUATION

癌症是一种具有巨大社会经济意义的顽固性疾病。 尽管在过去的治疗中已经实现了一些改进 几年来，仍然需要有效的药物来治疗全身性 治疗转移性疾病。植物是已被证实的有用的来源之一 化疗药物，以及发现这种药物的最集中的方法 试剂是由生物测定指导的分馏过程。在 这次国家天然产物药物合作发现的框架 小组，该项目将提供生物检测支持。在上一次 在项目期间，我们已经开发了一组人类肿瘤细胞系 包括Bc1(乳房)、Col2(结肠癌)、LU1(肺部)、HT-1080(肉瘤)、 MEL 2(黑色素瘤)，KB，多药耐药KB-V1，ZR-75-1(乳房)，LNCaP (前列腺)和A431(鳞状)细胞。KB-V1单元格的评估方法为 长春花碱存在和不存在时的植物提取物和分离物 建立逆转多药耐药的潜力 表型。此外，抗有丝分裂的潜力通常是 用培养的ASK细胞进行监测。我们已经在这些方面取得了成功 程序和结果数据与信息很好地结合在一起 通过其他成员执行的基于机制的分析获得的 国家协作天然产物药物发现小组。此外, 用这组细胞系获得的活性图谱是有价值的 在考虑更先进的活性菌株的发展。因此， 这些细胞系将继续用于即将到来的项目 句号。已添加到面板中的另一个单元格线是 指定税2-4。该细胞系的生长依赖于添加 紫杉醇的存在，所以紫杉醇类化合物的存在可以 在原油混合物中可辨别，该细胞系可用于 活性铅的生物测定定向分级。另外，因为它 明确需要一些行动机制的指示才能 正确评估新的植物菌株并鉴定其有效性 更高级的开发，机械化的评估将作为 这是这个项目的一部分。这些机制研究将被进行到 根据化学结构和在 体外活性图谱。作为一个额外的贡献，所有的分离物 由财团其他成员获得的信息将在测试中进行评估 此项目管理的系统，并将输入所有生成的数据 放到一个公共数据库中。总体而言，这个项目将继续专注于 提供一种临床上有用的癌症化疗药物 通过国家自然合作组织的共同努力 产品药物发现小组。

Cancer is a recalcitrant disease of enormous socioeconomic importance. Although some improvements in therapy have been realized over the past several years, efficacious drugs are still needed for the systemic treatment of metastatic disease. Plants are one proven source of useful chemotherapeutic agents, and the most focussed method of uncovering such agents is by the process of bioassay-guided fractionation. In the framework of this National Collaborative Natural Product Drug Discovery Group, this project will provide bioassay support. In the previous project period, we have developed a panel of human tumor cell lines comprised of BC1 (breast), Col2 (colon), Lu1 (lung), HT-1080 (sarcoma), Mel 2 (melanoma), KB, multidrug-resistant KB-V1, ZR-75-1 (breast), LNCaP (prostate), and A431 (squamous) cells. KB-V1 cells are evaluated with plant extracts and isolates in the presence and absence of vinblastine to establish the potential of reversing the multidrug-resistance phenotype. In addition, antimitotic potential has been routinely monitored with cultured ASK cells. We have had success with these procedures and the resulting data integrate well with the information obtained with mechanism-based assays performed by other members of the National Collaborative Natural Product Drug Discovery Group. In addition, the activity profile obtained with this panel of cell lines is of value in considering the more advanced development of active isolates. Thus, these cell lines will continue to be employed in the upcoming project period. One additional cell line that has been added to the panel is designated Tax 2-4. Growth of this cell line is dependent on the addition of taxol to the medium, so the presence of taxol-like compounds can be discerned in crude mixtures, and the cell line can be used for the bioassay-directed fractionation of active leads. In addition, since it is clear the some indication of mechanism of action is required in order to properly assess novel plant isolates and to appraise the validity of more advanced development, mechanistic evaluations will be performed as part of this project. These mechanistic studies will be performed to the extent that is warranted on the basis of chemical structure and the in vitro activity profile. As an additional contribution, all isolates obtained by other members of the consortium will be evaluated in the test systems managed by this project, and all resulting data will be entered into a common database. Overall, this project will remained focussed on the provision of a clinically useful cancer chemotherapeutic agent through the consolidated effort of the National Collaborative Natural Product Drug Discovery Group.